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21 May 2010

Cutaneous Fungal Infections
* Dermatophytosis - "ringworm" disease of the nails, hair, and/or stratum corneum of the skin caused by fungi called dermatophytes.
* Dermatomycosis - more general name for any skin disease caused by a fungus.

THE SKIN PLANTS
* Etiological agents are called dermatophytes - "skin plants". Three important anamorphic genera, (i.e., Microsporum, Trichophyton, and Epidermophyton), are involved in ringworm.
* Dermatophytes are keratinophilic - "keratin loving". Keratin is a major protein found in horns, hooves, nails, hair, and skin.
* Ringworm - disease called ‘herpes' by the Greeks, and by the Romans ‘tinea' (which means small insect larvae).

Infections by Dermatophytes
* Severity of ringworm disease depends on (1) strains or species of fungus involved and (2) sensitivity of the host to a particular pathogenic fungus.
* More severe reactions occur when a dermatophyte crosses non-host lines (e.g., from an animal species to man). Among dermatophytes there appears to be a evolutionary transition from a saprophytic to a parasitic lifestyle.
o Geophilic species - keratin-utilizing soil saprophytes (e.g., M. gypseum, T. ajelloi).
o Zoophilic species - keratin-utilizing on hosts - living animals (e.g., M. canis, T. verrucosum).
o Anthropophilic species - keratin-utilizing on hosts - humans (e.g., M. audounii, T. tonsurans)

Species found in different anamorphic genera are the cause of different clinical manifestations of ring worm
* Microsporum - infections on skin and hair (not the cause of TINEA UNGUIUM)
* Epidermophyton - infections on skin and nails (not the cause of TINEA CAPITIS)
* Trichophyton - infections on skin, hair, and nails.

Major sources of ringworm infection
* Schools, military camps, prisons.
* Warm damp areas (e.g., tropics, moisture accumulation in clothing and shoes). Historical note: More people were shipped out of the Pacific Theater in WWII back to U.S. because of ringworm infection then through injury.
* Animals (e.g., dogs, cats, cattle, poultry, etc.).

Diagnosis
* Note the symptoms.
* Microscopic examination of slides of skin scrapings, nail scrapings, and hair. Often tissue suspended in 10 % KOH solution to help clear tissue. Slides prepared this way are not permanent. These degrade rapidly due to presence of base.
* Isolation of the fungus from infected tissue.
* Proper treatment is dependent on diagnosis and prognosis.

CLINICAL MANIFESTATIONS OF RINGWORM SYMPTOMS AND TREATMENT
* tinea pedis - Athletes' foot infection
* between toes or toe webs (releasing of clear fluid) - 4th and 5th toes are most common.
* Soreness and itching of any part of the foot.
* In one study - 85 % of college students carried a ringworm fungus.
* Common disease but fairly recent was not recognized until late 19th century.
* Spread of disease correlated with introduction and generalized distribution of T. rubrum into Europe and America probably due to massive movement of peoples due to colonial occupation, slave trade, and World War II.
* Origin of T. rubrum may have been SE Asia or Africa.
* Fungi probably transmitted host to host through infected squames; flat, keratinised, dead cells shed from the outermost layer of a stratified squamous epithelium.
* Three causal agents, T. rubrum (source of inoculum comes from people with chronic infections, because fungus not long-lived in squames), T. mentagrophytes, and Epidermophyton floccosum (source of inoculum comes from long-lived arthrospores that reside in squames deposited in rugs and carpets (fomites).
* Three Grades of Infection
* Grade I - Subclinical
o An itching between toes, skin may be soft and macerated, blistering my occur.
o Treatment - keeping feet dry and clean, drying between the toes lightly each time you bathe to remove some skin. Application of fungicidal powders or ointments containing (1) salicylic acids to promote peeling of the skin and/or (2) tonaftate or other topical fungicides.
* Grade II
o Host is conscious of a burning sensation while walking and standing.
o Soaks are recommended (paints or liquids) such as 1:4000 KMnO4 (stains the skin purple) or topical fungicides.
o Remove clear liquid from blisters by having a doctor puncture near the base or unroofing the blister.
o Dusting powder in morning to help keep feet dry.

Tinea Pedis – Athlete’s Foot Infection
* Grade III
* Allergic reactions are sometimes associated with tinea pedis and other ringworm infections.
* dermatophytid - an "id" allergic reaction.
* toxins get into blood stream and reaches a site other than the site of infection.
* blistering occurs on fingers and hands.
* in diagnosis, rule out allergic reaction to poison ivy, detergents or other substances.
* during diagnosis, look for tinea (pedis, often) on the body.
* treat the primary site of infection where the antigen is being produced.
* treat secondary site - blisters.

Dermatophytid Reaction
* tinea corporis - body ringworm
* Generally restricted to stratum corneum of the smooth skin.
* Symptoms result form fungi metabolites such as toxin/allergens.
* Disease found throughout the world.
* Produces concentric or ring-like lesions on skin, and in severe cases these are raised and may become inflamed.
* All forms of tinea corporis caused by T. rubrum, T. mentagrophytes, T. tonsurans, M. canis, and M. audouinii are treatable with topical agent containing tolnaftate, ketoconazole, miconazole, etc...
* Disease transmitted through infected scales hyphae or arthroconidia on the skin.
* Also transmitted through direct contact between infected humans or animals, by fomites (any agent such a bedding or clothing capable of retaining a pathogen and transmitting to a new host).
* Transfer form on area to the body to another (from tinea pedis to tinea corporis).
* Tinea Corporis normally resolves itself in several months.
* T. verrucosum and T. violaceum infections require more vigorous treatment including cleaning of area to remove of scales and older fungicidal topical applications of ammoniated mercury ointment, 3 % salicylic and sulfuric acid, or tincture of iodine for several weeks.
* Widespread tinea corporis and more severe types (lesions) require systemic griseofulvin treatment (about 6 weeks for effective treatment).

Tinea corporis – body ringworm
* tinea cruris - ringworm of the groin and surrounding region
* More common in men than women.
* Infection seen on scrotum and inner thigh, the penis is usually not infected.
* Epidemics associated with grouping of people into tight quarters - athletic teams, troops, ship crews, inmates of institutions.
* Several causes of tinea cruris include T. rubrum (does not normally survive long periods outside of host), E. flocossum (usually associate with epidemics because resistant arthroconidia in skin scales can survive for years on rugs, shower stalls, locker room floors), T. mentagrophytes (usually of animal origin, such as rodents), and Microsporum gallinae (rarely seen - usually found on gallinaceous birds like turkeys and chickens).
* Predisposing factors include persistent perspiration, high humidity, irritation of skin from clothes, such as tight fitting underwear or athletic supporters, pre-existing disease, such as diabetes and obesity.
* Diagnosis
o If lesion "weep", it is likely caused by a yeast, such as, Candida albicans, and not by a dermatophyte, especially if infections are seen in a woman.
o KOH examination of skin scrapings.
o Culture of dermatophyte from skin scrapings.
* Treatment
o Tolnaftate (Tinactin trademark) treatment protocol for tinea corporis.
o Relief of symptoms occur within 3 days and treatment continued until all signs of disease are gone.
o Area is sensitive so the other care needs to be taken into to add to irritation of region.

Tinea Cruris – Jock Itch
* tinea unguium - ringworm of the nails
* Tinea unguium or onchomycosis can take two forms:
o Leukonychia mycotica - superficial white onychomycosis, invasion of fungus restricted to patches or pits on surface of the toenail.
o Invasive subungual dermatophytosis - lateral or distal edges first involved, followed by establishment of the infection beneath the nail plate. Invasion of nail plates by dermatophytes.
* Onychomycosis (infection of nails caused by non-dermatophytic fungi and yeasts)
* Most commonly caused by T. rubrum, then E. floccosum or other Trichophyton species.
* Resistant to treatment, rarely resolves spontaneously.
* Topical treatments - poor record of cure.
* Ablation - surgical or chemical removal of nail.
* Systemic griseofulvin therapy can lead to remission (usually a year or more of treatment required - results vary about 29 % cure rate).
* Use of other systemic antifungal (i.e., Lamisiltrademark or terbinafine HCl).
* Filing down the nail to paper thin consistency and soaking or painting with KMnO4 (1:4000), phenol, 10 % salicylic acid, or 1% iodine is useful adjunct to systemic griseofulvin treatment.

Tinea Unguium – Nail Infection
* tinea capitis - ringworm of the scalp, eyebrows and eyelashes
* Caused by species of Microsporum and Trichophyton.
* Fungus grows into hair follicle.
* Using a Wood's lamp, on hair Microsporum species tend to fluoresce green while Trichophyton species generally do not fluoresce.
* Lack of fluorescence does not mean it isn't Microsporum.
* Subculture any strands of hair that fluoresce to help identify the causal agent.
* Ectothrix infection - fragmentation of mycelium into conidia (called arthroconidia) around the hair shaft or just beneath the cuticle with destruction of the cuticle. This type of infection caused by M. audounii, M. canis, M. ferrugineum, T. mentagrophytes, T. verrucosum and T. megninii.
* Endothrix infection - arthroconidia formation occurs by fragmentation of hyphae with the hair shaft with destruction of the cuticle. This type of infection caused T. tonsurans (most common cause), T. violaceum, T. rubrum, and T. gourvillii. All these pathogen species are anthropophilic.
* "Gray patch ringworm" ectothrix common disease in children usually not associated with inflammation.
* Zoophilic and geophilic dermatophytes infections on man associate with inflammation. Microsporum canis, T. verrucosum, and T. mentagrophytes (zoophilic); M. gypseum and M. fulvum (geophilic species).
* "Id" reaction may occur.

Treatment of Tinea Capitis
* Ectothrix infections often resolve on their own.
* Endothrix infections my become chronic and may continue into adulthood.
* Topical treatments are ineffective (don't bother using tonaftate or topical griseofulvin)
* Fungistatic agents are somewhat effective (miconazole, clotrimazole) in combination to systemic administration of griseofulvin.
* Vigorous daily scrubs of scalp help removal of infectious debris. Do not use this treatment on patients with porphyria (an accumulation of blood pigment called porphyrins in blood stream and urine) or is hypersensitive to griseofulvin.

Tinea Capitis Gray Patch
Ectothrix and Endothrix
Fluorescing hair (under Wood's lamp) is seen in dogs and cats infected with some dermatophytes
Arthroconidia on hair
Microsporum canis
Teleomorph: Arthroderma otae
Microsporum gypseum
Epidermophyton floccosum
DERMATOPHYTES
* Trichophyton rubrum
* Infects nails and smooth skin (rarely found on hair).
* Most common and widely distributed dermatophyte on man and rarely isolated from animals, never from soils.
* No teleomorph (possibly lost in transition from saprophytic lifestyle to man).
* Resistant and persistent (some people become carriers for life).
* Slow-growing in culture.
* When intensely pigmented in culture the color is reminiscent of port burgundy wine or venous blood.
* Production of pigment increased, if fungus grown on corn meal agar.
* Microconidium are clavate or "teardrop" shape with a broad attachment point of the hyphae.
* Microconidia may develop on sides of macroconidium.
* In vitro - lack of hair penetrating organs, unlike T. mentagrophytes.
* T. violaceum grows poorly without thiamine. T. megninii grows poorly without L-histidine. T. rubrum requires neither thiamine or L- histidine.
* Trichophyton violaceum
* Attacks hair, scalp, skin and nails.
* Nail infections are persistent.
* Endothrix (black dot infection of scalp).
* Found in humans, rarely in animals.
* Disease has been reported in horses, cats, dogs, mice and pigeons.
* Very slow growing in culture with a waxy appearance.
* Colony deep violent in color, purplish pigment diffuses into media.
* Rarely produces microconidia and macroconidia.
* In culture this species requires thiamine for proper growth.
* Hyphae coarser in appearance than seen in other dermatophytes.
* Chlamydoconidia are seen in culture.
* Trichophyton verrucosum
* Associated with cattle ("barn itch").
* Large-spored ectothrix.
* Causes severer infections in humans on the scalp and beard.
* Very slow growing, no pigment on reverse to yellow.
* Grows best at 37 C.
* On unenriched media - chains of chlamydoconidia and antler-like hyphae.
* On thiamine-enriched media, produces many small microconidia and occasionally macroconidia are produced.

Hyponatremia
* Defined as sodium concentration < 135 mEq/L
* Generally considered a disorder of water as opposed to disorder of salt
* Results from increased water retention
* Normal physiologic measures allow a person to excrete up to 10 liters of water per day which protects against hyponatremia
* Thus, in most cases, some impairment of renal excretion of water is present
Causes
* Normal ADH response to low sodium is to be suppressed to allow maximally dilute urine to be excreted thereby raising serum sodium level
* Psuedohyponatremia – High blood sugar (DKA) or protein level (multiple myeloma) can cause falsely depressed sodium levels
* Causes of Hyponatremia can be classified based on either volume status or ADH level
o Hypovolemic, Euvolemic or Hypervolemic
o ADH inappropriately elevated or appropriately suppressed
ADH suppresion
ADH elevation
First step in Assessment: Are symptoms present?
* Hyponatremia can be asymptomatic and found by routine lab testing
* It may present with mild symptoms such as nausea and malaise (earliest) or headache and lethargy
* Or it may present with more severe symptoms such as seizures, coma or respiratory arrest

Presentation determines if immediate action is needed
* If severe symptoms are present, hypertonic saline needs to be administered to prevent further decline
* If severe symptoms are not present, can start by initiating fluid restriction and determining cause of hyponatremia
* Oral fluid restriction is good first step as it will prevent further drop in sodium
* NOTE: This does not mean that you can’t give isotonic fluids to someone who is truly volume depleted

Additional Tests
* TSH – high in hypothyroidism
* Cortisol – low in adrenal insufficiency, though may be inappropriately normal in infection/stressful state, therefore should get Corti-Stim test to confirm
* Head CT and Chest Xray – May see evidence of cerebral salt wasting or small cell carcinoma which can both cause hyponatremia
* Iatrogenic infusion of hypotonic fluids (“Surgeon sign”)
* Ecstasy use – increased water intake with inappropriate ADH secretion
* Underlying infections
* NSIAD – Nephrogenic syndrome of inappropriate antidiuresis – Hereditary disorder that presents with low sodium levels in newborn males with undetectable ADH levels
* Reset Osmostat – Occurs in elderly and pregnancy where regulated sodium set point is lowered

SIADH: Important concept to understand
Main diagnostic criteria for SIADH
Treatment is based on symptoms
Severe symptoms present
What if little to no symptoms are present?
Formulas that may help: How much sodium does the patient need?
* Sodium deficit = Total body water x (desired Na – actual Na)
* Total body water is estimated as lean body weight x 0.5 for women or 0.6 for men

How about an example:
What if the sodium increases too fast?
Risk Factors for demyelination
Treatment Options
Summary of Hyponatremia
Moving on to Hypernatremia
Causes of Hypernatremia
Symptoms of Hypernatremia
Diagnosis of Hypernatremia
Treatment of Hypernatremia
Summary of Hypernatremia

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